A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia
Abstract
1. Introduction
2. Ibrutinib
3. Acalabrutinib
4. Zanubrutinib
5. Pirtobrutinib
6. Overcoming Resistance to BTKi
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study | No. of Patients with PD | CLL Status | Drug | BTK and PLCG2 Mutations | VAF, % | Reference |
---|---|---|---|---|---|---|
Woyach et al., 2014 | 6 | R/R | Ibrutinib | BTK (5/6): C481S PLCG 2 (2/6): L845F, R665W, S707Y | nd | [26] |
Maddock et al., 2017 | 40 | R/R | Ibrutinib | BTK (37/40): C481S (34/37), C481F, C481A, C481R, PLCG 2 (7/40): L845F, R665W, S707Y, S707P, S707F, L845/846del, D993Y | 0.2–100.0 3.4–44.4 | [27] |
Ahn et al., 2017 | 13 | TN and R/R | Ibrutinib | BTK (7/13): C481S (7/7), C481F PLCG 2 (7/13): L845F, R665W, S707Y, P664S, 6NT del | 1.6–78.2 0.1–18.3 | [23] |
Kanagal-Shamanna et al., 2019 | 23 | R/R | Ibrutinib | BTL (16/23): C481S, C481F, C481Y, C481R, V537I PLCG2: 0/23 | 1.0–91.0 | [39] |
Bonfiglio et al., 2023 | 49 | TN and R/R | Ibrutinib | BTK (24/49): C481R, C481S, C481Y PLCG2 (14/49): D1140N, D993Y, M1141K, D993G, M1141R, L848R, D993H, L845F, R665W, S 707F, E1139G, D1140G | 1.8–79.5 1.7–32.7 | [29] |
Woyach et al., 2019 | 24 | R/R | Ibrutinib | BTK (11/24): C481S, C481Y, C481R, L528W, A428D PLCG2 (6/24) | 5.8 (median) | [49] |
46 | R/R | Acalabrutinib | BTK (31/46): C481S, C481Y, C481R, E41V PLCG2 (2/46) | 5.7 (median) | ||
Woyach et al., 2019 | 16 | TN and R/R | Acalabrutinib | BTK (11/16): C481S (10/11), C481R, C481Y, T474I PLCG2 2/16 | nd <3 | [18] |
Sun et al., 2023 | 20 | TN and R/R | Acalabrutinib | BTK 6/20: C481S 6/6, T474I PLCG 4/20 | 2.0–46.0 1.0–8.0 | [48] |
Blombery et al., 2022 | 24 | R/R | Ibrutinib | BTK (24/24): C481S (24/24), C481A, C481F, C418T, T474I, L528W | 1.0–79.0 | [55] |
13 | R/R | Zanubrutinib | BTK (10/13): C481S (10/13), L528W (7/10), C418T | 2.0–87.0 | ||
Brown et al., 2023 | 28 | R/R | Ibrutinib | BTK 3/28: C481S (3/3), D43H PLCG2 (2/28) | 0.5–8.0 | [19] |
24 | R/R | Zanubrutinib | BTK (5/24): C481S (4/5), C481Y, C481F, C481R, L528W, A428D PLCG2 (0/9) | 1.0–74.0 | ||
Handunnetti et al., 2019 | 4 | TN and R/R | Zanubrutinib | BTK (4/4): C481 (4/4), L528W (4/4) | L528W: 34.9 (median) C418: 9.1 (median) | [56] |
Wang et al., 2022 | 9 | R/R | Pirtobrutinib | BTK (7/9): V416L, M437R, T474I, L528W PLCG2 (0/9) | nd | [61] |
Brown et al., 2023 | 86 | R/R | Pirtobrutinib | BTK (38/86): T474I, T474F, T474S, T474L, T474Y, L528W, C481S, C481R, C481Y PLCG2 (6/86) | nd | [64] |
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Wiśniewski, K.; Puła, B. A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia. Int. J. Mol. Sci. 2024, 25, 5246. https://doi.org/10.3390/ijms25105246
Wiśniewski K, Puła B. A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences. 2024; 25(10):5246. https://doi.org/10.3390/ijms25105246
Chicago/Turabian StyleWiśniewski, Kamil, and Bartosz Puła. 2024. "A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia" International Journal of Molecular Sciences 25, no. 10: 5246. https://doi.org/10.3390/ijms25105246
APA StyleWiśniewski, K., & Puła, B. (2024). A Review of Resistance Mechanisms to Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences, 25(10), 5246. https://doi.org/10.3390/ijms25105246